Integrative Review of Genetic Factors Influencing Neurodevelopmental Outcomes in Preterm Infants
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Updated: Apr 3, 2026
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Lisa M Blair1, Rita H Pickler2, Cindy Anderson1
1The Ohio State University, Columbus, OH, USA.
Insights
Genetic factors increase neurodevelopmental risks in preterm infants without rare genetic disorders. Research identified 43 genes and copy number variants linked to outcomes like cognition and autism spectrum disorder.
Area of Science:
- Genetics
- Neurodevelopmental Biology
- Pediatrics
Background:
- Preterm infants face heightened risks for neurodevelopmental issues, potentially exacerbated by gene-environment interactions.
- While genetic links to atypical development are emerging, genomic risk profiles are not yet standard for infants without diagnosed genetic disorders.
Purpose of the Study:
- To review and synthesize current evidence on genetic associations with neurodevelopmental outcomes in preterm infants lacking rare genetic diseases.
- To identify candidate genes and genetic variants implicated in the neurodevelopment of this vulnerable population.
Main Methods:
- An integrative review design synthesized data from 29 English-language, peer-reviewed articles (primary research or meta-analyses) published between July 2009 and July 2014.
- Searches included electronic and hand-search strategies to identify relevant human studies.
Main Results:
- Forty-three genes and large deletion copy number variants were associated with diverse neurodevelopmental outcomes.
- These outcomes included cognitive function, attention, perception, psychiatric disorders, autism spectrum disorder, cerebral palsy, infant behavior, and brain architecture alterations.
Conclusions:
- Creating comprehensive genetic risk profiles is challenging due to inconsistent evidence, methodological issues, and lack of replication.
- Promising areas for future research include large copy number variants and specific genes like MET, NRG3, and SLC6A4, supported by multiple high-quality studies.
Abstract:
Preterm infants are at elevated risk for a host of neurodevelopmental problems, including disorders that appear later in life. Gene-environment interactions and prematurity may combine to increase the risk for poor neurodevelopmental outcomes. Increasing evidence supports a genetic link to risk for atypical development; however, no genomic risk profiles are currently used for infants without apparent genetic disorders. The purpose of this review was to synthesize recent evidence of genetic associations with atypical neurodevelopmental outcomes that may affect preterm infants who do not have a rare genetic disease. Electronic and hand-search strategies were used to find relevant articles that were English-language, peer-reviewed primary research or meta-analysis reports published between July 2009 and July 2014, involving human participants. Articles included in the analysis (N = 29) used a wide range of study designs and methodologies, complicating the analysis. An integrative-review design was used to synthesize the data. Numerous genes (n = 43) and additional large deletion copy number variants were associated with neurodevelopmental outcomes, including cognition, attention, perception, psychiatric disease, autism spectrum disorder, cerebral palsy, infant behavior, and alterations in brain architecture. The creation of genetic risk profiles for complex disorders of neurodevelopment is presently hindered by inconsistent genetic-association evidence, methodological considerations, reporting problems, and lack of replication. However, several avenues of investigation offer promise, including large (>100 kb) copy number variants and the candidate genes MET, NRG3, and SLC6A4, each of which were reported to have associations with neurodevelopmental outcomes in multiple, high-quality studies.
